phosphotyrosine-binding domain

{{Short description|Protein domain}}

{{Pfam box

| Symbol = PTB

| Name = Phosphotyrosine-binding domain

| image = PDB 1wvh EBI.jpg

| width =

| caption = Structure of the PTB domain of tensin1.{{cite journal |vauthors=McCleverty CJ, Lin DC, Liddington RC |title=Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions |journal=Protein Sci. |volume=16 |issue=6 |pages=1223–9 |date=June 2007 |pmid=17473008 |pmc=2206669 |doi=10.1110/ps.072798707 }}

| Pfam= PF08416

| InterPro= IPR013625

| SMART=

| Prosite =

| SCOP =

| TCDB =

| OPM family=

| OPM protein=

| CDD= cd00934

| PDB=

{{PDB3|1wvh}}A:1607-1738

}}

{{Infobox protein family

| Symbol = IRS

| Name = PTB domain (IRS-1 type)

| image = PDB 1irs EBI.jpg

| width =

| caption = irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, nmr, minimized average structure

| Pfam = PF02174

| Pfam_clan =

| InterPro = IPR002404

| SMART = PTBI

| PROSITE =

| MEROPS =

| SCOP = 1cli

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD = cd01204

}}

In molecular biology, phosphotyrosine-binding domains are protein domains which bind to phosphotyrosine.

The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 ({{Pfam|PF00017}}) domain and a region similar to the tumour suppressor PTEN.{{cite journal |vauthors=Chen H, Ishii A, Wong WK, Chen LB, Lo SH |title=Molecular characterization of human tensin |journal=Biochem. J. |volume=351 |issue= 2|pages=403–11 |date=October 2000 |pmid=11023826 |pmc=1221376 |doi= 10.1042/0264-6021:3510403}} The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.{{cite journal |author=Lo SH |title=Tensin |journal=Int. J. Biochem. Cell Biol. |volume=36 |issue=1 |pages=31–4 |date=January 2004 |pmid=14592531 |doi= 10.1016/S1357-2725(03)00171-7}}

The phosphotyrosine-binding domain of insulin receptor substrate-1 is not related to the phosphotyrosine-binding domain of tensin.

Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain and a phosphotyrosine binding (PTB) domain. The PTB domains facilitate interaction with the activated tyrosine-phosphorylated insulin receptor. The PTB domain is situated towards the N terminus. Two arginines in this domain are responsible for hydrogen bonding phosphotyrosine residues on an Ac-LYASSNPApY-NH2 peptide in the juxtamembrane region of the insulin receptor. Further interactions via "bridged" water molecules are coordinated by residues an Asn and a Ser residue.{{cite journal | vauthors = Eck MJ, Dhe-Paganon S, Trub T, Nolte RT, Shoelson SE | title = Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor | journal = Cell | volume = 85 | issue = 5 | pages = 695–705 |date=May 1996 | pmid = 8646778 | doi = 10.1016/S0092-8674(00)81236-2| s2cid = 8896348 | doi-access = free }} The PTB domain has a compact, 7-stranded beta-sandwich structure, capped by a C-terminal helix. The substrate peptide fits into an L-shaped surface cleft formed from the C-terminal helix and strands 5 and 6.{{cite journal | vauthors = Zhou MM, Huang B, Olejniczak ET, Meadows RP, Shuker SB, Miyazaki M, Trub T, Shoelson SE, Fesik SW | title = Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain | journal = Nat. Struct. Biol. | volume = 3 | issue = 4 | pages = 388–93 |date=April 1996 | pmid = 8599766 | doi = 10.1038/nsb0496-388| s2cid = 41440041 }}